Wanshui Yang1,2, Yanan Ma2,3, Yue Liu2,4, Stephanie A Smith-Warner5,6, Tracey G Simon7,8,9, Dawn Q Chong10, Qibin Qi11, Jeffrey A Meyerhardt12, Edward L Giovannucci2,5,6, Andrew T Chan2,8,9, Xuehong Zhang2. 1. Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, China. 2. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 3. Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, China. 4. Center for Evidence-Based Chinese Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. 5. Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 6. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 7. Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston. 8. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston. 9. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston. 10. National Cancer Centre Singapore, Singapore. 11. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. 12. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Abstract
IMPORTANCE: Increased intake of whole grain and dietary fiber has been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for hepatocellular carcinoma (HCC). Therefore, we hypothesized that long-term intake of whole grains and dietary fiber may be associated with lower risk of HCC. OBJECTIVE: To assess the associations of whole grain and dietary fiber intake with the risk of HCC. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) in 125 455 participants from 2 cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study. EXPOSURES: Intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) were collected and updated almost every 4 years using validated food frequency questionnaires. MAIN OUTCOMES AND MEASURES: Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression model after adjusting for most known HCC risk factors. RESULTS: After an average follow-up of 24.2 years, we identified 141 patients with HCC among 125 455 participants (77 241 women and 48 214 men (mean [SD] age, 63.4 [10.7] years). Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC. CONCLUSIONS AND RELEVANCE: Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.
IMPORTANCE: Increased intake of whole grain and dietary fiber has been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for hepatocellular carcinoma (HCC). Therefore, we hypothesized that long-term intake of whole grains and dietary fiber may be associated with lower risk of HCC. OBJECTIVE: To assess the associations of whole grain and dietary fiber intake with the risk of HCC. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) in 125 455 participants from 2 cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study. EXPOSURES: Intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) were collected and updated almost every 4 years using validated food frequency questionnaires. MAIN OUTCOMES AND MEASURES: Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression model after adjusting for most known HCC risk factors. RESULTS: After an average follow-up of 24.2 years, we identified 141 patients with HCC among 125 455 participants (77 241 women and 48 214 men (mean [SD] age, 63.4 [10.7] years). Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC. CONCLUSIONS AND RELEVANCE: Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.
Authors: Lyn M Steffen; David R Jacobs; Maureen A Murtaugh; Antoinette Moran; Julia Steinberger; Ching-Ping Hong; Alan R Sinaiko Journal: Am J Epidemiol Date: 2003-08-01 Impact factor: 4.897
Authors: S Chasan-Taber; E B Rimm; M J Stampfer; D Spiegelman; G A Colditz; E Giovannucci; A Ascherio; W C Willett Journal: Epidemiology Date: 1996-01 Impact factor: 4.822
Authors: Alan J Flint; Frank B Hu; Robert J Glynn; Majken K Jensen; Mary Franz; Laura Sampson; Eric B Rimm Journal: Am J Clin Nutr Date: 2009-07-01 Impact factor: 7.045
Authors: S Salvini; D J Hunter; L Sampson; M J Stampfer; G A Colditz; B Rosner; W C Willett Journal: Int J Epidemiol Date: 1989-12 Impact factor: 7.196
Authors: John C Mathers; Faye Elliott; Finlay Macrae; Jukka-Pekka Mecklin; Gabriela Möslein; Fiona E McRonald; Lucio Bertario; D Gareth Evans; Anne-Marie Gerdes; Judy W C Ho; Annika Lindblom; Patrick J Morrison; Jem Rashbass; Raj S Ramesar; Toni T Seppälä; Huw J W Thomas; Harsh J Sheth; Kirsi Pylvänäinen; Lynn Reed; Gillian M Borthwick; D Timothy Bishop; John Burn Journal: Cancer Prev Res (Phila) Date: 2022-09-01
Authors: Jiali Zheng; Carrie R Daniel; Rikita I Hatia; Janice Stuff; Ahmed A Abdelhakeem; Asif Rashid; Yun Shin Chun; Prasun K Jalal; Ahmed O Kaseb; Donghui Li; Manal M Hassan Journal: Hepatology Date: 2021-08-26 Impact factor: 17.425
Authors: Shehnaz K Hussain; Tien S Dong; Vatche Agopian; Joseph R Pisegna; Francisco A Durazo; Pedram Enayati; Vinay Sundaram; Jihane N Benhammou; Mazen Noureddin; Gina Choi; Walid S Ayoub; Venu Lagishetty; David Elashoff; Marc T Goodman; Jonathan P Jacobs Journal: Nutrients Date: 2020-05-13 Impact factor: 5.717
Authors: Evan Y W Yu; Anke Wesselius; Siamak Mehrkanoon; Maree Brinkman; Piet van den Brandt; Emily White; Elisabete Weiderpass; Florence Le Calvez-Kelm; Marc Gunter; Inge Huybrechts; Fredrik Liedberg; Guri Skeie; Anne Tjonneland; Elio Riboli; Graham G Giles; Roger L Milne; Maurice P Zeegers Journal: Am J Clin Nutr Date: 2020-11-11 Impact factor: 7.045